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NMSU's lone toxicologist tries to find the rhythm of breast cancer

After new epidemiological research found an increased risk of breast cancer associated with altered sleep patterns, an NMSU researcher decided to further investigate the 24-hour biological rhythm in breast cells.



NMSU toxicologist Aaron Rowland uses the Kronos Dio machine in his research on finding circadian rhythms in breast tissue cells. The machine measures the rhythms by monitoring the radiance of cells. (NMSU photo by Darren Phillips)

Although he has submitted three different grant proposals for continued research on this pattern, known as a circadian rhythm, and its influence on hormone levels within cells, Aaron Rowland, assistant professor of toxicology in the NMSU Department of Chemistry and Biochemistry, said he has high hopes for the latest one, submitted to the U.S. Department of Defense in November for $75,000.

"Research suggests that each cell type exhibits a roughly 24-hour cycle which regulates important cellular functions like controlling hormone levels and cell fate," Rowland said. "So, far, these rhythms have been demonstrated in a small number of isolated populations of human cells derived from peripheral tissues like bone, fat, skin and liver cells. But no one has yet to demonstrate the circadian rhythm in cultured breast cells, those grown in a laboratory dish."

Through the research, Rowland said he and his team hope to determine if disrupting these rhythms in cells plays a role in carcinogenesis, or the process of normal cells transforming into cancerous ones.

So, Rowland said, when women alter their sleep pattern and the circadian rhythm, like when working a night shift for example, it can put them at higher risk of breast cancer. This disruption was recently acknowledged by the World Health Organization's International Agency for Research on Cancer (IARC) as potentially carcinogenic to humans.

"It is possible that cellular changes in these rhythms alter the hormonal balance within cells, making them vulnerable," Rowland said. "There is some indication already that a hormone involved in regulating circadian rhythms, Melatonin, influences estrogen signaling. And, changes in estrogen signaling have been linked to some forms of breast cancer."

One aim of the research is to understand the signaling processes involved in the start and spread of these rhythms in cultured breast tissue cells. If Rowland can determine the basic processes that influence these rhythms, he will be able to understand the environmental factors that may influence them as well. This could lead to the development of pharmaceuticals to re-establish a healthy normal rhythm. Another aim is to examine the disruption and then determine if it is even related to carcinogenesis.

"If the process works in cultured cells, then there is the potential use of a rat model," Rowland said. That rat model belongs to co-investigator Todd Thompson, a researcher from the University of New Mexico. Rowland and Thompson submitted a grant proposal in October to the Cowboys for Cancer Selection Committee at the UNM Cancer Research and Treatment Center.

Rowland is preparing another grant proposal in collaboration with the former NMSU computer science department head, Desh Ranjan, to continue their work to understand and model circadian rhythms in human cell cultures. This collaborative effort is being prepared as one of the projects in the NMSU CREST Center for Bioinformatics and Computational Biology proposal. That proposal will be due in February. The $150,000 to $200,000-a-year grant will support circadian rhythm-related research conducted over a five-year period.

An important tool Rowland uses to conduct this research is called the Kronos Dio, a real-time luminescence machine that indirectly measures circadian rhythms by monitoring the radiance of uniquely tagged human cells in a culture dish.

"It's invaluable in examining circadian rhythms in cultured cells," Rowland said.

Rowland's background is in lung toxicology, so he describes these preliminary research efforts on breast cancer as his "branching out project." He said he should hear back from the Department of Defense in May on the proposal. That program is a congressionally directed medical research program that focuses on funding unique approaches and new avenues for understanding breast cancer.